A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip. Erythema nodosum occasionally raises problems with regard to aetiological diagnosis. It is characterised by painful erythematous nodular lesions, usually on the lower legs. It has various causes.

• Leprosy. Erythema nodosum leprosum forms a single entity, to be distinguished from classical erythema nodosum. It occurs as a complication in multibacillary leprosy. Systemic inflammation is usually prominent. It is not always easy to differentiate this leprosy type 2 reaction from an upgrading reaction (leprosy reaction type 1).
• Tuberculosis can be accompanied by erythema nodosum. Do not confuse this with Bazin’s erythema induratum, which also occurs on the lower leg. A tuberculous aetiology is assumed. It should also not be confused with lupus vulgaris.
• Sarcoidosis is one of the most frequent causes of erythema nodosum. Chest X-ray is indicated for detecting lesions of the lung parenchyma and hilar lymphadenopathy. Erythema nodosum with bilateral hilar adenopathy is also known as Löfgren's syndrome.
• Medication. Erythema nodosum can be elicited by medications such as sulphonamides and dapsone. The latter is used for treating leprosy and Pneumocystis carinii infections in AIDS patients. Similarly, there is a suspicion that oral contraceptives may induce this condition in some women.
• Infections. Streptococcal and Yersinia enterocolitica infections are seldom complicated by erythema nodosum. Chlamydia infections (incl. Chlamydia pneumoniae), brucellosis, psittacosis, sleeping sickness (West African trypanosomiasis), lymphogranuloma inguinale and cat scratch disease (Rochalimaea henselae, now renamed Bartonella henselae) are likewise rarely complicated by this cutaneous abnormality. Various deep mycoses such as histoplasmosis and coccidiomycosis can elicit erythema nodosum lesions.
• Inflammatory intestinal diseases such as Crohn's disease and ulcerative colitis. Pyoderma gangrenosum is another complication of these diseases.
• Systemic diseases such as polyarteritis nodosa can be accompanied by erythema nodosum lesions. Behçet's disease can be accompanied by erythema nodosum. Genital and oral ulcers, together with arthritis, iritis and neurological symptoms suggest the diagnosis.

A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip. Circular, migrating or non-migrating, transient serpiginous erythema frequently raises diagnostic problems.

• In tinea corporis (catherine wheel) there is invasion of the stratum corneum by dermatophytes. A skin scraping should be obtained for mycological investigation. Tinea imbricata (tokelau) is a fungal infection with a typical appearance (multiple concentric rings).
• Cutaneous larva migrans (syn. larva cutanea migrans) due to Ancylostoma braziliense and larva currens due to Strongyloides stercoralis cause serpiginous skin lesions and in practice pose no diagnostic problem. Gnatostomiasis (Gnatostoma spinigerum) can likewise cause a more deeply seated larva cutanea migrans. Subcutaneous migration of a Loa loa female is obviously different from Calabar swelling (oedema, pain, reddening, warm sensation) which likewise occurs in loasis.
• Erythema chronicum migrans is caused by infection with Borrelia burgdorferi (Lyme disease). There is often a case history of a tick bite. Secondary metastatic skin lesions can occur. Joint pain, cardiac conduction disorders and neurological symptoms are serious complications. Serological diagnosis is not easy.
• Leprosy, especially during leprosy reactions, can cause bewildering lesions.
• Trypanids produce transient erythema with indefinite outline that occurs in West African trypanosomiasis. They can occur anywhere, but are most frequently observed on the torso. The lesions can be large (more than 10 cm in diameter) and are triggered by local heat. Oedema without erythema will also occasionally be observed on the face. High temperature, splenomegaly and enlarged lymph nodes in the cervical area suggest the diagnosis. Serology and detection of trypanosomes are essential.
• Secondary syphilis can cause annular skin lesions, often on the face. The lesions do not migrate. Lues serology is essential.
• Erythema marginatum is a transient erythema and is one of the major Jones’ criteria for the diagnosis of acute rheumatic fever. The lesions are usually very short-lived, but usually recur on the torso and the proximal parts of the limbs. The other major criteria are carditis, arthritis, chorea and subcutaneous noduli. These do not occur all at the same time.
• Erythema annulare centrifugum is a red, flat or slightly elevated lesion that slowly spreads. It usually occurs on the buttocks or the thighs. A cause usually cannot be found, though it is occasionally observed as an immunological reaction in cutaneous mycoses (tinea).
• Granuloma annulare is an idiopathic condition. The edges are slightly papular and elevated. It is an important differential diagnosis in tuberculoid leprosy. There is usually little erythema.
• Erythema gyratum repens should lead to suspicion of an underlying malignity. It is characterised by numerous concentric red circles with a wave-like / undulating erythema. It is often compared with the grain of wood.
• Urticaria is accompanied by substantial pruritus (itching). The diagnosis is usually immediately obvious, though the aetiology is often much more difficult to determine.
• Rare causes of serpiginous skin lesions are elastosis perforans serpiginosa with preferred locations on the neck and the elbow folds (especially in connective tissue diseases such as Ehlers-Danlos and Marfan syndrome). Psoriasis gyrata, lupus erythematosus, sarcoidosis, Jessner-Kanof disease and cutaneous T-cell lymphoma also cause strikingly shaped skin lesions. Necrolytic migrating erythema is very rare. It is associated with alpha-cell tumours of the pancreas (glucagonoma). The disease causes red spots with the formation of central blisters and cutaneous erosions. The preferred locations are the groins and perineum and around the mouth.

A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip. There are numerous cosmopolitan conditions that cause nodular skin lesions (sebum cysts, dermoid cysts, lipoma, metastasis, etc.). A survey of a few of the more unusual causes follows below.

• Leishmaniasis. Cutaneous leishmaniasis will usually form a painless ulcer, though a nodular form also occurs. Diffuse cutaneous leishmaniasis with non-ulcerating nodules is a very chronic disease. The lesions contain numerous amastigotes. Dermal leishmaniasis can occur in post-kalar azar after the patient has had visceral leishmaniasis. Discoloured spots and painless noduli are observed. Post-kalar azar leishmaniasis is frequent in India, less frequent Africa and practically non-existent in South and Central America.
• Lepromatous leprosy. Noduli, plaques or diffuse infiltration of the skin with Mycobacterium leprae characterise this disease. The pathogenic organism is present in large numbers and can be detected with Kinyoun staining (variant of Ziehl-Neelsen staining).
• Kaposi’s sarcoma. This malignant tumour is characterised by proliferation of capillaries and perivascular connective tissue cells. A viral aetiology has been established. Generalised Kaposi’s sarcoma is nowadays practically synonymous with AIDS. Endemic Kaposi is not HIV-related and tends to provoke very chronic lesions on hands and feet/lower legs. In AIDS the reddish-purple nodules occur both on the skin and internally, in the mouth, lungs, stomach and pleura. The lesions must be differentiated from angiosarcoma, haematoma, haemangioma, angiokeratoma and granuloma pyogenicum. In 1996 it was shown that repeated intralesional injections of hCG (a pregnancy hormone) can induce apoptosis in the tumour cells, with clinical improvement. Usually chemotherapy and/or radiotherapy is used.
• Chronic bartonellosis or verruga peruviana, caused by infection with Bartonella bacilliformis. This rare disease is restricted to South America. In its acute stage there is a febrile haemolytic anaemie (Oroya fever). In the chronic stage that usually follows some 6 to 14 weeks after the acute stage a miliary, nodular and mular form is differentiated. This last form can look like a granuloma pyogenicum. These lesions can persist for months and even years.
• Cutaneous bacillary angiomatosis in AIDS patients. Probably secondary to infection with Rochalimaea henselae (now renamed Bartonella henselae), an organism related to rickettsia. The organism can occasionally be demonstrated on biopsy with Warthin-Starry staining. Specific serology can be carried out
• Cutaneous dirofilariosis. This is an isolated and often asymptomatic nodule, caused by infection with Dirofilaria (Nochtiella) repens or with Dirofilaria tenuis. Infection with Dirofilaria immitis causes lung lesions rather than skin nodules. Resection is diagnostic and curative. No microfilariae are present in the blood.
• Cysticercosis. If ova of Taenia solium, the porcine tapeworm, are ingested, cysticercosis can follow. The larvae can get established in many organs (muscle, brain, dermis). The palpable cutaneous nodules are painless. There is a high risk of neurocysticercosis.
• Onchocerciasis. Subcutaneous noduli, pruritus, lesions of the eye and lymphadenopathy ("hanging groin") are typical. Sowda is a form of onchocerciasis that occurs in Yemen. The diagnosis is made by demonstrating the microfilariae or by resecting a nodule containing macrofilaria.
• Treponematosis. Juxta-articular noduli in endemic treponematosis such as framboesia (yaws, pian). The raspberry-shaped skin lesions in the early stages usually raise no diagnostic problem. Osteitis will frequently be present (nasal bones, tibia). Residual hypopigmentation of the skin lesions is the rule.
• Mycosis. Lobomycosis and chromomycosis are mycoses that can cause nodular skin lesions. Lobomycosis resembles keloids. Lesions caused by chromomycosis frequently ulcerate and look like warts. Biopsies are essential.
• Rhinosporidiosis can cause polyp-like growths localised on mucosae or mucocutaneous zones (very rarely on the skin itself). Sporangia are very clearly observable on biopsy.
• Acute rheumatic fever is still frequent in tropical countries. It can occur only a few weeks after a throat infection with Lancefield group A streptococci, e.g. Streptococcus pyogenes. Subcutaneous noduli are one of the principal Jones’ diagnostic criteria. Noduli appear some weeks after the carditis and migratory arthritis. Both erythema marginatum and noduli are rare. The nodules are small and painless. They are found especially on tendons and on sites where bone lies just under the skin (extensor side of elbows, knees, wrists, occipitum, spines of the vertebrae). The skin nodules in acute rheumatic fever are related to Aschoff noduli in the heart.
• Osler noduli in subacute bacterial endocarditis. Pea-sized red or purple noduli on fingers, hands, toes and feet. They are probably of embolic origin and lead to an intracutaneous vasculitis. They disappear spontaneously after a few days. High temperature, cardiac murmour, petechiae, splinter haemorrhages (especially in nailbed), clubbing, Janeway lesions (transient red maculae) on palms of the hands and soles of the feet, Roth spots on the retina (white centre surrounded by red ring) should be looked for in physical examination. Neurological complications are frequent (septic emboli). Formation of mycotic aneurysmata is rare.
• Rheumatoid nodules (elbows, knees, fingers) are firm, 5 to 40 mm diameter nodules that are present in approximately 20% of patients with rheumatoid arthritis (in only 6% with Still’s disease). Rheumatoid nodules, splenomegaly and selective neutropenia occur frequently in Felty’s syndrome. Rheumatoid noduli must not be confused with gout tophi or with Heberden- and Bouchard nodules in arthrosis (on respectively distal and proximal interphalangeal joints).
• Mycobacterium marinum infection sometimes occurs after cleaning of an aquarium. A nodular lesion can be formed (finger, hand). This will frequently ulcerate. Acid-fast bacilli can be detected in a direct smear or biopsy. Mycobacterial culture is indicated. Sporotrichosis, nocardiosis and cat scratch disease (Rochalimaea henselae, now renamed Bartonella henselae; Afipia felis) are important differential diagnoses. Mycological culture, serology and anatomopathology will be useful here.
• Leukaemia. Maculopapular, papulonodular and occasionally purely nodular infiltrative skin lesions can occur in monocytic leukaemia. These can precede the leukaemic abnormalities in the peripheral blood. Cutaneous lymphoma can likewise cause infiltrative nodular lesions.

A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip.

• Mycoses. Paracoccidioidomycosis or South American blastomycosis is frequently accompanied by lesions on the lips and nose. Histoplasmosis is another cause. Systemic cryptococcosis often causes lesions on the nose, e.g. in AIDS patients.
• Espundia (mucocutaneous leishmaniasis). An important differential diagnosis in South America. Classical cutaneous leishmaniasis can also occur on the face.
• Treponematosis (e.g. gangosa in yaws, gumma of tertiary syphilis). Serology is essential.
• Leprosy, especially lepromatous leprosy.
• Other mycobacterial diseases, especially tuberculosis and Buruli ulcer.
• Noma (cancrum oris).
• Neoplastic such as in a basocellular or epidermoid carcinoma, non-Hodgkin lymphoma, midline granuloma, Kaposi’s sarcoma and Burkitt’s lymphoma.
• Mouth ulcers and mouth abscesses, as well as lesions on the tongue and in the oesophagus, can be caused by the nematode Gongylonema pulchrum. Such infections are very rare. A very thin but long worm (6-14 cm in length) can be removed from the lesions.
• Balamuthia mandrillaris can cause facial lesions.

A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip.

• Tunga penetrans (sandfleas). These insects tend to burrom in the sole of the feet or under the nails. Surinfectons can lead to very serious complications.
• Leprosy, complicated by Charcot joints and trophic / neuropathic ulcers is an important cause of lesions of the sole of the feet.
• Neurosyphilis. Besides looking for other stigmata of syphilis, serology should be performed on serum and cerebrospinal fluid.
• Diabetes mellitus. The most common cause in the West. In some communities, diabetes is very common. One can easily state that the is a globalpandemic of diabetes going on right now.
• Consider other causes of Charcot joints (neuropathic joints) with chronic pressure sores.
• Foreign bodies (thorns, sea urchin spines, …)
• Infected dishydrotic eczema, occasionally triggered as an intradermal reaction to fungal infections, e.g. dermatophytes (tinea)
• Norwegian scabies. Check for immunodepression, such as AIDS, HTLV-1 and other conditions.
• Plantar warts, especially if they are surinfected due to scratching.
• Maduramycosis. More often localised around the ankle, but can occur anywhere. The fistulae secrete typical granules, not to be confounded with bothryomycosis.
• Tuberculosis.
• Buruli ulcer (mycobacterial)

The localisation of the ulcer as well as the appearance (undermined or raised borders, purulent covering) is important. Is it a painful lesion? It should be determined whether it is an acute or a chronic problem. A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip. In the following review both tropical and cosmopolitan diseases will be mentioned.

• Primary syphilis: usually painless lesion with enlarged inguinal lymph nodes and a positive serology. Initially the serology may still be negative. Dark-field microscopy of material from the lesion is carried out less frequently. The ulcer heals spontaneously even without therapy.
• Chancroid, caused by Haemophilus ducreyi. This is usually a painful lesion and the inguinal lymph nodes contain a large amount of pus. These can fistulate though the skin. Diagnosis relies on bacterial culture.
• Donovaniosis (Calymmatobacterium granulomatosis) or granuloma inguinalis is rare. The intracellular Gram-negative bacillus cannot be cultured in vitro. The clinical appearance is that of an ulcerated granulomatous painless lesion. Biopsies and smears are used for diagnosis.
• Lymphogranuloma venereum (Nicolas-Favre disease). This disease is caused by Chlamydia trachomatis serotypes L1-2-3. One to three weeks after contact an inoculation chancre appears in the form of a small painless spot or herpetiform ulcer. This is followed a few weeks later by adenopathy (inguinal buboe ) that can form multiple fistulae (differential diagnosis with Crohn's disease, actinomycosis, tuberculosis). These local symptoms are accompanied by fever, general malaise and arthralgias. There is occasionally rectal involvement that can develop into rectal stenosis (especially in women). Elephantiasis of the (male) genitals can be a late sequel. Mouth and pharynx lesions are rare, but can occur after oral sexual contact.
• Herpes genitalis: usually painful and recurrent. The virus can be cultured (use correct material for sampling and for transport)
• Fournier’s scrotal gangrene.
• Spreading intestinal amoebiasis (Entamoeba histolytica) or infection via anal sex. Trophozoites can be shown at the edge of the lesion.
• Behçet's syndrome: systemic disease characterised by recurrent arthritis accompanied by eye lesions (keratitis, iritis), painful genital ulcers that heal with scar formation, sometimes cerebral symptoms and recurrent thrombophlebitis.
• Bartholinitis with breakthrough of an abscess can cause a painful lesion on the labia. Gonococci should be searched for.
• Carcinoma, e.g. epidermoid, occasionally also Kaposi’s sarcoma.
• Tuberculosis
• Trauma

A problem that occurs during or after a trip does not necessarily need to have a causal connection with that trip.

• Furuncles (boils), wound infection and ecthyma caused by Streptococcus pyogenes or Staphylococcus aureus are frequent. Myiasis can easily be confused with furuncles, especially in the early stages.
• Inoculation chancre of syphilis and rickettsioses (tick-bite fever and scrub typhus).
• Tertiary treponematoses (syphilis, yaws). Serology is essential.
• Cutaneous anthrax is rare. The diagnosis can be considered if there is contact with hides followed by black scab formation with a substantial erythematous zone. The very large Gram-positive bacteria are characteristic.
• Cutaneous tularaemia is rare, but can lead to an ulceroglandular syndrome.
• Cutaneous diphtheria or veld sore is initially painful. Neurological complications are rare, in contrast to pharyngeal diphtheria.
• Tropical ulcer. Initially painful and foul-smelling. Thereafter formation of a very chronic, atonic ulcer.
• Bartonellosis and cat scratch disease occasionally provokes skin ulcers.
• Mycobacterial: M. marinum, M. ulcerans or Buruli ulcer, tuberculosis, leprosy.
• Leishmaniasis (cutaneous): painless. Amastigotes are found in the edges of the wound.
• Cutaneous amoebiasis due to E. histolytica (rare).
• Trypanomata (sleeping disease inoculation chancre and chagoma) tend to heal spontaneously.
• Herpes simplex
• Various fungi such as sporotrichosis, blastomycosis, cryptococcosis, histoplasmosis and Penicillium marneffei can cause cutaneous ulcers. Sporotrichosis is one of the few mycoses for which diagnosis relies almost exclusively on culture, due to the rarity of the organisms on smears.
• Abdominal wall abscesses with ulceration : Actinomycosis fistula, osteomyelitis, oesophagostomiasis (abdominal wall), breakthrough of liver abscess due to E. histolytica, (perianal) Crohn's disease.
• Guinea worm (dracunculosis), usually in the calf of the leg or the ankle/foot region.
• A subcutaneous abscess, e.g. due to Wuchereria bancrofti, can give rise to an ulcer.
• Trauma with or without cellulitis. Spider bites (Loxosceles sp, but not Latrodectus sp) can cause local necrosis of the skin. Many venomous snake bites cause tissue necrosis at the site of the bite. Wound infections occur more easily in the tropics than in areas with a temperate climate.
• A neuropathic origin (leprosy, diabetes, syphilis) should be considered for ulcers on the soles of the feet, though foreign objects and sand fleas (Tunga penetrans) are more often the cause.
• Venous stasis ulcer.
• Sickle cell ulcer (lower legs) in homozygotes. Zinc deficiency is frequent here and must be treated.
• Cutaneous vasculitis
• Neoplasia, occasionally as complication by e.g. a chronic tropical ulcer. Melanoma is more frequent in people who were exposed to a lot of sunlight (lot of UV-irradiation of the skin).
• Necrobiosis lipoidica, pyoderma gangrenosum, erythema multiforma, Behçet syndrome, cholesterol emboli and cryoglobulinaemia are rare causes of skin lesions.
• Endemic pemphigus foliaceus is not a problem in travellers, but tends to occur in people who reside for longer periods in an endemic area.

This syndrome is defined by the presence of a skin lesion with associated regional lymphadenopathy. The classic cause is tularemia (Francisella tularensis), acquired by contact with an infected rabbit or tick. More common causes include pyogenic bacteria including streptococcal infection, cat-scratch disease (Bartonella henselae), cutaneous anthrax, subcutaneous and deep mycoses and mycobacterial infections (e.g. Mycobacterium tuberculosis, M. marinum). Cleaning fish tanks - aquaria- is a clue obtained during anamnesis, increasing the likelihood of an infection with Mycobacterium marinum. Syphilis, chancroid and lymphogranuloma venereum (LGV) can produce an ulceroglandular syndrome. Sometimes a neoplastic process is responsible.